Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.